Rosucard, pills 20mg, 60pcs

Composition

Each 20 mg film coated tablet contains: Active ingredient: rosuvastatin-20,000 mg (in the form of rosuvastatin calcium-20,800 mg); Excipients: the core: lactose monohydrate-120,000 mg, microcrystalline cellulose-90,800 mg, croscarmellose sodium-2,400 mg, colloidal silicon dioxide-1,200 mg, magnesium stearate-4,800 mg; film-coated: hypromellose 2910/5 – 5,000 mg, macrogol 6000-0,800 mg, titanium dioxide-0.650 mg, talc-0.950 mg, iron oxide red dye-0.065 mg

Pharmacological action

Hypolipidemic agent from the statin group. Selective competitive inhibitor of Z-hydroxy-Z-methylglutaryl coenzyme A (HMG-CoA) reductase, an enzyme that converts HMG-CoA to mevalonate, a cholesterol precursor. Increases the number of low-density lipoprotein (LDL) receptors on the surface of hepatocytes, which leads to increased uptake and catabolism of LDL, inhibition of the synthesis of very low-density lipoproteins( VLDL), reducing the total concentration of LDL and VLDL. Reduces the concentration of cholesterol-LDL cholesterol-lipoproteins high density (XC-nalit), cholesterol-VLDL, total cholesterol, triglycerides (TG), TG-VLDL, apolipoprotein b (Apob), reduces the ratio of cholesterol-LDL/HDL-C, total cholesterol/HDL – C, HS-nalit/HDL-C, Apob/apolipoprotein A-1 (Apoa-I) increases the concentration of HDL-C and Apoa-I. The hypolipidemic effect is directly proportional to the prescribed dose. The therapeutic effect appears within 1 week after the start of therapy, after 2 weeks it reaches 90% of the maximum, by 4 weeks it reaches its maximum and then remains constant. It is effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia (regardless of race, gender, or age), including those with diabetes mellitus and familial hypercholesterolemia. In 80% of patients with hypercholesterolemia type IIa and IIb (Fredrickson classification) with an average initial LDL-C concentration of about 4.8 mmol / L, the LDL-C concentration reaches values of less than 3 mmol/l when taking the drug at a dose of 10 mg. In patients with homozygous familial hypercholesterolemia, taking the drug at a dose of 20 mg and 40 mg, the average decrease in LDL-C concentration is 22%. The additive effect is observed in combination with fenofibrate (for reducing the concentration of TG and nicotinic acid in lipid-lowering doses (at least 1 g / day) (for reducing the concentration of HDL-C). Pharmacokinetics of absorption The maximum concentration (Cmax) of rosuvastatin in blood plasma is reached approximately 5 hours after taking the drug. Absolute bioavailability is approximately 20%. Systemic exposure to rosuvastatin increases in proportion to the dose. Pharmacokinetic parameters do not change with daily use. Distribution penetrates the placental barrier. Rosuvastatin is absorbed mainly by the liver, which is the main site of cholesterol synthesis and LDL-C metabolism. The volume of distribution is 134 liters. Binding to plasma proteins (mainly albumin) is approximately 90%. Metabolizmbiotransformed in the liver to a small extent (about 10%), being a non-core substrate for cytochrome P 450 isoenzymes. As with other HMG-CoA reductase inhibitors, a specific membrane transporter, an organic anion – transporting polypeptide (OATP), is involved in the hepatic uptake of the drug 1 In 1, which plays an important role in its hepatic elimination. The main isoenzyme involved in the metabolism of rosuvastatin is CYP2C9. The isoenzymes CYP2C19, CYP3A4, and CYP2D6 are less involved in metabolism. The main metabolites of rosuvastatin are N-dismethyl and lactone metabolites. N-dismethyl is approximately 50% less active than rosuvastatin, and the lactone metabolites are pharmacologically inactive. More than 90% of the pharmacological activity in inhibiting circulating HMG-CoA reductase is provided by rosuvastatin, the rest by its metabolites. Elimination About 90% of the rosuvastatin dose is excreted unchanged through the intestines, the remainder through the kidneys. The half-life (T 1/2) is approximately 19 hours, does not change with increasing dose of the drug. The average plasma clearance is approximately 50 l / h (coefficient of variation 21.7%). In patients with mild to moderate renal insufficiency, the plasma concentration of rosuvastatin or N-dismethyl does not change significantly. In patients with severe renal insufficiency (creatinine clearance less than 30 ml/min), the concentration of rosuvastatin in blood plasma is 3 times higher, and N-dismethyl – 9 times higher than in healthy volunteers. The plasma concentration of rosuvastatin in patients undergoing hemodialysis is approximately 50% higher than in healthy volunteers. In patients with a Child-Pugh score of 7 or lower, there was no increase in rosuvastatin T 1/2; in patients with Child-Pugh scores of 8 and 9, there was a 2-fold increase in T 1/2. There is no experience of using the drug in patients with more severe hepatic impairment. Gender and age do not have a clinically significant effect on the pharmacokinetics of rosuvastatin. Ethnic groupspharmacokinetic parameters of rosuvastatin depend on race: the area under the concentration-time curve (AUC) in representatives of the Mongoloid race (Japanese, Chinese, Filipinos, Vietnamese and Koreans) is 2 times higher than in representatives of the Caucasian race. In the case of Indians, the average value of AUC and C max increased by 1.3 times.

Indications

• Primary hypercholesterolemia (Fredrickson type IIa), including heterozygous hereditary hypercholesterolemia or mixed (combined) hypercholesterolemia (Fredrickson type IIB), as an adjunct to diet and other non-drug measures (exercise and weight loss) if diet therapy and non-drug measures are ineffective;
• Homozygous form of hereditary hypercholesterolemia and when diet therapy and other lipid-lowering treatments are not effective enough (for example, LDL apheresis), or if such treatments are not suitable for the patient.
• Hypertriglyceridemia (Fredrickson type IV) as a dietary supplement.
• To slow the progression of atherosclerosis as an adjunct to diet in patients who are indicated for therapy to reduce the concentration of total cholesterol and LDL-C.
• Prevention of major cardiovascular complications (stroke, heart attack, arterial revascularization) in adult patients without clinical signs of coronary heart disease (CHD), but with an increased risk of its development (age over 50 years for men and over 60 years for women, increased concentration of C-reactive protein (≥ 2 mg / l) in the presence of at least one of the additional risk factors, such as arterial hypertension, low HDL-C concentration, smoking, family history of early

Contraindications

• Hypersensitivity to rosuvastatin or other components of the drug;
• Liver diseases in the active phase or a steady increase in the serum activity of “hepatic” transaminases (more than 3 times compared to the upper limit of normal) of unknown origin, liver failure (severity from 7 to 9 points on the Child-Pugh scale);
• An increase in the concentration of creatinine phosphokinase (CPK) in the blood by more than 5 times compared to the upper limit of normal (ULN);
• Hereditary diseases, such as lactose intolerance, lactase deficiency, or glucose-galactose malabsorption (due to the presence of lactose in the composition).
• Severe renal impairment (creatinine clearance less than 30 ml / min);
• Myopathy;
• Patients predisposed to the development of myotoxic complications;
• Simultaneous use of cyclosporine;
• Co-use with HIV protease inhibitors;
• Women of reproductive age who do not use adequate methods of contraception;
• Pregnancy and lactation;
• Age up to 18 years (efficacy and safety have not been established).

Side effects

The frequency of adverse reactions was determined according to the following gradation (classification of the World Health Organization): very often-more than 1/10, often-from more than 1/100 to less than 1/10, infrequently – from more than 1/1000 to less than 1/100, rarely-from more than 1/10000 to less than 1/1000, very rarely – from less than 1/10000, including individual messages. an unspecified frequency. From the central nervous system: often-headache, dizziness, asthenic syndrome; very rarely-peripheral neuropathy, memory loss. From the digestive system: often – nausea, constipation, abdominal pain; infrequently-vomiting; rarely-pancreatitis; very rarely-hepatitis, jaundice; unspecified frequency-diarrhea. From the respiratory system: infrequently-cough, dyspnoea. From the endocrine system: often – type 2 diabetes mellitus. From the musculoskeletal system: often-myalgia; very rarely-arthralgia; rarely-myopathy (including myositis), rhabdomyolysis. Allergic reactions: infrequently-pruritus, urticaria, rash; rarely-angioedema. Skin and subcutaneous tissue: not specified frequency – Stevens-Johnson syndrome, peripheral edema. From the urinary system: often-proteinuria (with a frequency of more than 3% in patients receiving a dose of 40 mg), which decreases during therapy and is not associated with the occurrence of kidney disease, urinary tract infection; very rarely – hematuria. Laboratory parameters: infrequently-a transient dose-dependent increase in the activity of serum creatine phosphokinase (CPK), with an increase of more than 5 times compared to the upper limit of normal, therapy should be temporarily suspended; rarely – a transient increase in the activity of aspartate aminotransferase and alanine aminotransferase.As with other HMG-CoA reductase inhibitors, the frequency of occurrence is dose-dependent, and side effects are usually mild and resolve on their own. When using ROSUCARD®, changes in the following laboratory parameters were noted: increased glucose concentration, bilirubin, alkaline phosphatase activity, gamma-glutamyltransferase. The following side effects have been reported with other statins: depression, insomnia, decreased potency. Isolated cases of interstitial lung disease have been reported with prolonged use of rosuvastatin.

Interaction

Concomitant use of rosuvastatin and cyclosporine does not affect the plasma concentration of cyclosporine, but the effect of rosuvastatin is enhanced (its excretion slows down, AUC increases by 7 times, With_max-by 11 times).. Erythromycin enhances intestinal motility, which leads to a decrease in the effect of rosuvastatin (AUC decreases by 20% and_max by 30%). In patients receiving vitamin K antagonists (for example, warfarin), monitoring of the international normalized ratio (INR) is recommended, since starting therapy with rosuvastatin or increasing the dose of the drug may lead to an increase in INR, and discontinuing rosuvastatin or reducing its dose may lead to a decrease in it. Gemfibrozil enhances the effect of rosuvastatin (increases C_max and AUC by 2 times). Simultaneous use of rosuvastatin and antacids containing aluminum and magnesium hydroxide leads to a decrease in the plasma concentration of rosuvastatin by about 50%. This effect is less pronounced if antacids are applied 2 hours after taking rosuvastatin. Concomitant use of rosuvastatin and oral contraceptives increases the AUC of ethinyl estradiol and AUC of norgestrel by 26% and 34%, respectively, which should be taken into account when selecting the dose of oral contraceptives. Pharmacokinetic data on the simultaneous use of rosuvastatin and hormone replacement therapy are not available, therefore, a similar effect cannot be excluded when using this combination. The results of studies showed that rosuvastatin is neither an inhibitor nor an inducer of the action of cytochrome P450 isoenzymes. Rosuvastatin is a non-core substrate for these isoenzymes. There were no clinically significant interactions with drugs such as fluconazole, ketoconazole, and itraconazole associated with cytochrome P450 metabolism. There was no clinically significant interaction of rosuvastatin with digoxin or fenofibrate, Gemfibrozil, other fibrates, and hypolipidemic doses of nicotinic acid (at least 1 g/day) increased the risk of myopathy when co-administered with other HMG-CoA reductase inhibitors. Possibly due to the fact that they can cause myopathy and when used as monotherapy. Couse of rosuvastatin and ezetimibe did not result in changes in AUC or_cmax both medications. The use of HIV protease inhibitors (human immunodeficiency virus) with rosuvastatin can significantly enhance the effect of rosuvastatin. A pharmacokinetic study of co-use of 20 mg rosuvastatin and a combination of two HIV protease inhibitors (400 mg lopinavir / 100 mg ritonavir) in healthy volunteers resulted in approximately two – and five-fold increases in AUC(0-24) and_cmax, respectively. Therefore, co-use of rosuvastatin with HIV protease inhibitors is not recommended in patients infected with HIV.

How to take, course of use and dosage

Inside, without chewing or grinding, swallow whole, washed down with water, at any time of the day, regardless of food intake. Before starting drug therapy Rosucard the patient should start following a standard lipid-lowering diet and continue to follow it during treatment. The dose of the drug should be selected individually, depending on the indications and therapeutic response, taking into account current generally accepted recommendations for target lipid levels. If you need to take the drug at a dose of 5 mg, you should divide the 10 mg tablet into two parts according to the risk. Recommended starting dose of the drug Rozukard for patients starting to take the drug, or for patients transferred from taking other HMG – CoA reductase inhibitors, is 5 or 10 mg 1 time per day. When choosing the initial dose, the patient’s cholesterol level should be guided and the risk of developing cardiovascular complications should be taken into account, as well as the potential risk of side effects should be evaluated. If necessary, the dose of the drug can be increased after 4 weeks. Due to the possible development of side effects when taking a dose of 40 mg compared to lower doses of the drug (see the section “Side effects”) final titration to a maximum dose of 40 mg should only be performed in patients with severe hypercholesterolemia and a high risk of cardiovascular complications (especially in patients with hereditary hypercholesterolemia), who did not reach the target cholesterol level at a dose of 20 mg, and who will be under medical supervision. Patients with hepatic insufficiency In patients with hepatic insufficiency with values on the Child-Pugh scale below 7 points of dose adjustment Rosacard is not required. Patients with renal insufficiency In patients with mild renal insufficiency, no dose adjustment is required. An initial dose is recommended Rosucarda – 5 mg per day. Use in patients with severe renal insufficiency (creatinine clearance less than 30 ml/min). Rosucarda is contraindicated. Use in patients with moderate renal insufficiency (creatinine clearance 30-60 ml / min). Rosucarda at a dose of 40 mg per day is contraindicated (see the section “Contraindications”). Special populations. Elderly patients In patients over 65 years of age, no dose adjustment is required. Patients with a predisposition to myopathyapplication Rosucarda at a dose of 40 mg per day is contraindicated in patients with a predisposition to myopathy (see the section “Contraindications”). When prescribing doses of 10 mg and 20 mg per day, the recommended initial dose is Rosucarda for this group of patients is 5 mg per day. Ethnic groupsin the study of the pharmacokinetic parameters of rosuvastatin, an increase in the systemic concentration of the drug was noted in representatives of the Mongolian race (see the section “Pharmacokinetics”). This fact should be taken into account when prescribing Rosukarda to patients of the Mongoloid race. When prescribing doses of 10 and 20 mg, the recommended starting dose is Rosucarda for this group of patients is 5 mg per day. Application Rosucarda at a dose of 40 mg per day in representatives of the Mongoloid race is contraindicated (see the section “Contraindications”). When making an appointment Rosucarda with gemfibrozil dose should not exceed 10 mg per day.

Overdose

With simultaneous use of several daily doses, the pharmacokinetic parameters of rosuvastatin do not change. Treatment: there is no specific treatment, symptomatic therapy is performed to maintain the functions of vital organs and systems. Monitoring of liver function and CKD activity is necessary. Hemodialysis is ineffective.

Special instructions

During treatment, especially during the period of dose adjustment of Rosucard®, the lipid profile should be monitored every 2-4 weeks and the dose of the drug should be changed if necessary.

It is recommended to determine liver function indicators before the start of therapy and 3 months after the start of therapy. Rosucard® should be discontinued or the dose of the drug should be reduced if the level of hepatic transaminase activity in the blood serum is 3 times higher than the ULN.

When using the drug Rozukard® at a dose of 40 mg, it is recommended to monitor the indicators of renal function.

In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, treatment of the underlying diseases should be performed before starting treatment with Rosucard®.

In patients with existing risk factors for rhabdomyolysis, it is necessary to consider the ratio of expected benefit and potential risk and conduct clinical monitoring throughout the course of treatment.

The patient should be informed of the need to immediately inform the doctor about cases of muscle pain, muscle weakness or spasms, especially in combination with malaise and fever.

In such patients, CPK activity should be determined. Therapy should be discontinued if CKD activity is significantly increased (more than 5 times higher than ULN) or muscle symptoms are severe and cause daily discomfort. If symptoms disappear and CPK activity returns to normal, consideration should be given to re-prescribing Rozucard® or other HMG-CoA reductase inhibitors in smaller doses, with careful monitoring of the patient.

Determination of CPK activity should not be performed after intense physical exertion or in the presence of other possible reasons for its increase, which may lead to incorrect interpretation of the results. If the initial CPK activity is significantly increased, a second measurement should be performed after 5-7 days — you can not start therapy if the repeated test confirms the initial CPK activity (5 times higher than normal).

Routine monitoring of CPK activity in the absence of the above symptoms is not advisable.

An increased incidence of myositis and myopathy has been reported in patients treated with other HMG-CoA reductase inhibitors in combination with fibrates (including gemfibrozil), cyclosporine, nicotinic acid, azole antifungal drugs, protease inhibitors, and macrolide antibiotics.It is necessary to carefully weigh the ratio of expected benefit and potential risk when using Rosucard® together with fibrates or nicotinic acid (in lipid-lowering doses-1 g / day), simultaneous use of gemfibrozil is not recommended.

In most cases, proteinuria decreases or disappears during therapy and does not mean the occurrence of acute or exacerbation of existing kidney disease. Evaluation of renal function should be performed during routine examination of patients receiving a dose of 40 mg.

Drugs of the statin class can cause an increase in the concentration of glucose in the blood. In some patients with a high risk of developing diabetes mellitus, such changes may lead to its manifestation, which is an indication for the appointment of hypoglycemic therapy. However, the reduction in the risk of vascular diseases with statins exceeds the risk of developing diabetes, so this factor should not serve as a reason for discontinuing statin treatment. Patients at risk (fasting blood glucose concentration 5.6-6.9 mmol / l, BMI >30 kg / m2, hypertriglyceridemia, a history of arterial hypertension) should be monitored and regularly monitored for biochemical parameters.

Co-use of rosuvastatin and HIV protease inhibitors is not recommended.

Isolated cases of interstitial lung disease have been reported with prolonged use of rosuvastatin. If interstitial lung disease is suspected, discontinue therapy with Rosucard®.

When studying the pharmacokinetic parameters of rosuvastatin, an increase in the systemic concentration of the drug was noted in representatives of the Mongolian race (see “Pharmacokinetics”). This fact should be taken into account when prescribing Rosucard® to these patients.

Influence on the ability to drive vehicles and work with mechanisms. Caution should be exercised when driving vehicles and engaging in activities that require increased concentration and speed of psychomotor reactions (dizziness may occur during therapy).

Form of production

Film-coated tablets.

Storage conditions

At a temperature not exceeding 25 ° C in the original packaging.

Shelf

life is 2 years.

Active ingredient

Rosuvastatin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets